LESIONED LOW-DENSITY-LIPOPROTEIN IN ATHEROSCLEROTIC APOLIPOPROTEIN E-DEFICIENT TRANSGENIC MICE AND IN HUMANS IS OXIDIZED AND AGGREGATED

We analyzed lesioned LDL in both atherosclerotic humans and in the apo E deficient (E degrees) mice and compared its characteristics to plas ma LDL. Lesioned LDL, in comparison to plasma LDL, was minimally oxidi zed and aggregated. Upon incubation of E degrees-aortic lesions with ( 125)[I]-labeled LDL, a time-dependent oxidation of the lipoprotein occ urred as evident by a rapid and substantial elevation in LDL-associate d TBARS from 0.2 to 10.3 and 14.5 nmoles of MDA equivalents/mg LDL pro tein after 2 and 24 hours of incubation, respectively. Only minimal LD L aggregates could be detected after 2 hours of incubation. Extensive LDL aggregation (15%), however, occurred after 24h of incubation. Simi lar results were obtained on using human lesioned aortas. We conclude that both oxidation and aggregation of lesioned LDL could be the resul t of aortic lesioned-induced modification of the lipoprotein, and both of these modified forms of LDL can further contribute to the accelera tion of the atherosclerotic process. (C) 1995 Academic Press, Inc.